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FEBS Lett. 2004 Dec 3;578(1-2):90-4.

Protein kinase Akt/PKB phosphorylates heme oxygenase-1 in vitro and in vivo.

Author information

1
Instituto de Investigaciones Biomedicas A. Sols UAM-CSIC and Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, Madrid 28029, Spain.

Abstract

Heme oxygenase-1 (HO-1) is a stress response protein that protects cells against diverse noxious stimuli. Although regulation of HO-1 occurs mainly at the transcriptional level, its posttranslational modifications remain unexplored. We have identified a putative consensus sequence for phosphorylation by Akt/PKB of HO-1 at Ser188. Recombinant human and rat HO-1, but not mutant HO-1(S188A), are phosphorylated in vitro by Akt/PKB. Isotopic 32P-labeling of HEK293T cells confirmed that HO-1 is a phosphoprotein and that the basal HO-1 phosphorylation is increased by Akt1 activation. HO-1(S188D), a single point mutant equivalent to the phosphorylated protein, exhibited over 1.6-fold higher activity than wild type HO-1. Fluorescence resonance energy transfer (FRET) studies indicated that HO-1(S188D) bound to cytochrome P450 reductase (CPR) and biliverdin reductase (BVR) with a slightly lower Kd than wild-type HO-1. Although the changes in activity are small, this study provides the first evidence for a role of the survival kinase Akt in the regulation of HO-1.

PMID:
15581622
DOI:
10.1016/j.febslet.2004.10.077
[Indexed for MEDLINE]
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